ITPRIP Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited population of human lung adenocarcinoma cells with targeted disruption of the ITPRIP gene. This polyclonal knockout model provides a loss-of-function system for exploring ITPRIP??s roles in calcium signaling and cancer biology. The cells are supplied as an unselected pool, representing a heterogeneous knockout background suited for population-level assays and avoiding clonal artifacts.
The NCI-H1975 parental line originates from a non-smoking female patient with lung adenocarcinoma and carries both EGFR L858R and PIK3CA G118D mutations. These epithelial cells are sensitive to EGFR tyrosine kinase inhibitors and are widely employed as a model for EGFR-driven non-small cell lung cancer, providing a clinically relevant host for gene perturbation studies.
ITPRIP physically interacts with IP3 receptors (ITPR1, ITPR2, ITPR3) and modulates their sensitivity to IP3, governing endoplasmic reticulum calcium release. Through this regulatory function, ITPRIP influences cytosolic calcium dynamics that activate calpain, calcineurin, and calmodulin-dependent cascades. Downstream, ITPRIP impacts apoptotic signaling by shifting the Bcl-2/Bax balance and intersects with autophagy pathways through factors such as Beclin-1. Upstream, ITPRIP integrates signals from cytosolic calcium, IP3, and EGFR-mediated inputs.
In the EGFR-mutant NCI-H1975 background, ITPRIP knockout disrupts calcium-dependent crosstalk between oncogenic EGFR signaling and cellular outcomes. Loss of ITPRIP may recalibrate apoptotic thresholds and autophagy-mediated survival, potentially altering sensitivity to EGFR inhibitors. This model thus enables dissection of how ITPRIP-governed calcium regulation contributes to proliferation, survival, and drug response in lung adenocarcinoma.
These cells are suitable for calcium flux fluorimetry (Fura-2, Fluo-4), Western blotting for ITPR1/2/3, co-immunoprecipitation of ITPRIP complexes, and functional assays including Annexin V/caspase-3/7 apoptosis measurements, LC3-based autophagy flux analysis, and cell proliferation or EGFR inhibitor sensitivity testing. For additional details or technical assistance, contact Ascent Research.
